Association between funding source, methodological quality and research outcomes in randomized controlled trials of synbiotics, probiotics and prebiotics added to infant formula: a systematic review.

BACKGROUND: There is little or no information available on the impact of funding by the food industry on trial outcomes and methodological quality of synbiotics, probiotics and prebiotics research in infants. The objective of this study was to compare the methodological quality, outcomes of food industry sponsored trials versus non industry sponsored trials, with regards to supplementation of synbiotics, probiotics and prebiotics in infant formula. METHODS: A comprehensive search was conducted to identify published and unpublished randomized clinical trials (RCTs). Cochrane methodology was used to assess the risk of bias of included RCTs in the following domains: 1) sequence generation; 2) allocation concealment; 3) blinding; 4) incomplete outcome data; 5) selective outcome reporting; and 6) other bias. Clinical outcomes and authors' conclusions were reported in frequencies and percentages. The association between source of funding, risk of bias, clinical outcomes and conclusions were assessed using Pearson's Chi-square test and the Fisher's exact test. A p-value < 0.05 was statistically significant. RESULTS: Sixty seven completed and 3 on-going RCTs were included. Forty (59.7%) were funded by food industry, 11 (16.4%) by non-industry entities and 16 (23.9%) did not specify source of funding. Several risk of bias domains, especially sequence generation, allocation concealment and blinding, were not adequately reported. There was no significant association between the source of funding and sequence generation, allocation concealment, blinding and selective reporting, majority of reported clinical outcomes or authors' conclusions. On the other hand, source of funding was significantly associated with the domains of incomplete outcome data, free of other bias domains as well as reported antibiotic use and conclusions on weight gain. CONCLUSION: In RCTs on infants fed infant formula containing probiotics, prebiotics or synbiotics, the source of funding did not influence the majority of outcomes in favour of the sponsors' products. More non-industry funded research is needed to further assess the impact of funding on methodological quality, reported clinical outcomes and authors' conclusions.

Probiotics, prebiotics infant formula use in preterm or low birth weight infants: a systematic review.

BACKGROUND: Previous reviews (2005 to 2009) on preterm infants given probiotics or prebiotics with breast milk or mixed feeds focused on prevention of Necrotizing Enterocolitis, sepsis and diarrhea. This review assessed if probiotics, prebiotics led to improved growth and clinical outcomes in formula fed preterm infants. METHODS: Cochrane methodology was followed using randomized controlled trials (RCTs) which compared preterm formula containing probiotic(s) or prebiotic(s) to conventional preterm formula in preterm infants. The mean difference (MD) and corresponding 95% confidence intervals (CI) were reported for continuous outcomes, risk ratio (RR) and corresponding 95% CI for dichotomous outcomes. Heterogeneity was assessed by visual inspection of forest plots and a chi² test. An I² test assessed inconsistencies across studies. I²> 50% represented substantial heterogeneity. RESULTS: Four probiotics studies (N=212), 4 prebiotics studies (N=126) were included. Probiotics: There were no significant differences in weight gain (MD 1.96, 95% CI: -2.64 to 6.56, 2 studies, n=34) or in maximal enteral feed (MD 35.20, 95% CI: -7.61 to 78.02, 2 studies, n=34), number of stools per day increased significantly in probiotic group (MD 1.60, 95% CI: 1.20 to 2.00, 1 study, n=20). Prebiotics: Galacto-oligosaccharide/Fructo-oligosaccharide (GOS/FOS) yielded no significant difference in weight gain (MD 0.04, 95% CI: -2.65 to 2.73, 2 studies, n=50), GOS/FOS yielded no significant differences in length gain (MD 0.01, 95% CI: -0.03 to 0.04, 2 studies, n=50). There were no significant differences in head growth (MD -0.01, 95% CI: -0.02 to 0.00, 2 studies, n=76) or age at full enteral feed (MD -0.79, 95% CI: -2.20 to 0.61, 2 studies, n=86). Stool frequency increased significantly in prebiotic group (MD 0.80, 95% CI: 0.48 to 1.1, 2 studies, n=86). GOS/FOS and FOS yielded higher bifidobacteria counts in prebiotics group (MD 2.10, 95% CI: 0.96 to 3.24, n=27) and (MD 0.48, 95% CI: 0.28 to 0.68, n=56). CONCLUSIONS: There is not enough evidence to state that supplementation with probiotics or prebiotics results in improved growth and clinical outcomes in exclusively formula fed preterm infants.

Synbiotics, probiotics or prebiotics in infant formula for full term infants: a systematic review.

BACKGROUND: Synbiotics, probiotics or prebiotics are being added to infant formula to promote growth and development in infants. Previous reviews (2007 to 2011) on term infants given probiotics or prebiotics focused on prevention of allergic disease and food hypersensitivity. This review focused on growth and clinical outcomes in term infants fed only infant formula containing synbiotics, probiotics or prebiotics. METHODS: Cochrane methodology was followed using randomized controlled trials (RCTs) which compared term infant formula containing probiotics, prebiotics or synbiotics to conventional infant formula with / without placebo among healthy full term infants. The mean difference (MD) and corresponding 95% confidence intervals (CI) were reported for continuous outcomes, risk ratio (RR) and corresponding 95% CI for dichotomous outcomes. Where appropriate, meta-analysis was performed; heterogeneity was explored using subgroup and sensitivity analyses. If studies were too diverse a narrative synthesis was provided. RESULTS: Three synbiotic studies (N = 475), 10 probiotics studies (N = 933) and 12 prebiotics studies (N = 1563) were included. Synbiotics failed to significantly increase growth in boys and girls. Use of synbiotics increased stool frequency, had no impact on stool consistency, colic, spitting up / regurgitation, crying, restlessness or vomiting. Probiotics in formula also failed to have any significant effect on growth, stool frequency or consistency. Probiotics did not lower the incidence of diarrhoea, colic, spitting up / regurgitation, crying, restlessness or vomiting. Prebiotics in formula did increase weight gain but had no impact on length or head circumference gain. Prebiotics increased stool frequency but had no impact on stool consistency, the incidence of colic, spitting up / regurgitation, crying, restlessness or vomiting. There was no impact of prebiotics on the volume of formula tolerated, infections and gastrointestinal microflora. The quality of evidence was compromised by imprecision, inconsistency of results, use of different study preparations and publication bias. AUTHORS' CONCLUSIONS: There is not enough evidence to state that supplementation of term infant formula with synbiotics, probiotics or prebiotics does result in improved growth or clinical outcomes in term infants. There is no data available to establish if synbiotics are superior to probiotics or prebiotics.

Application of evidence on probiotics, prebiotics and synbiotics by food industry: a descriptive study.

BACKGROUND: This study assessed how the food industry applies the knowledge and evidence gained from synbiotics, probiotics or prebiotics research in infants, on the general paediatric population. This study also explored: what happens after the clinical trials using infant formula are completed, data is published or remains unpublished; the effectiveness and type of medium the formula manufacturers use to educate consumers on probiotic, prebiotic or synbiotic infant formula. FINDINGS: This was a descriptive study (a survey) that used a structured questionnaire. All listed companies that manufacture and / or market food products with added probiotics, prebiotics or synbiotics for infants were identified and invited to participate. People responsible for research and development were invited to participate in the survey. A letter of invitation was sent to selected participants and if they expressed willingness to take part in the study, a questionnaire with a written consent form was sent. Descriptive statistics and associations between categorical variables were to be tested using a Chi-square test, a p < 0.05 was statistically significant.A total of 25 major infant formulas, baby food manufacturers were identified, invited to participate in the survey. No company was willing to participate in the survey for different reasons: failure to take any action 5 (20%), decision to participate indefinitely delayed 2 (8%), sensitivity of requested information 3 (12%), company does not conduct clinical trials 1 (4%), company declined without further information 4 (16%), erroneous contact information 6 (24%), refusal by receptionists to forward telephone calls to appropriate staff 3 (12%), language barrier 3 (12%), company no longer agrees to market research 1 (4%). CONCLUSION: Due to a poor response rate in this study, no conclusion could be drawn on how the food industry applies evidence gained through probiotics, prebiotics or synbiotics research on infants for the benefit of the general paediatric population. More information and greater transparency is needed from the infant formula manufacturers on how they apply the evidence gained from the research on probiotics, prebiotics and synbiotics on infants.